Perimenstrual psychiatric hospitalization: case report and literature review.

Despite the fact that menstrual psychosis has been described since the eighteenth century, there are only about 80 cases reported in the literature. The knowledge and awareness about the disorder remain poor, leading to inaccurate diagnoses and suboptimal treatment. This is the case of a 25-year-old woman with recurrent hospitalizations for mental status changes including psychotic phenomena and catatonia that appeared to follow a cyclical pattern that correlated with her menstrual periods, with complete symptom resolution and return to her usual level of functioning between episodes despite continued treatment with antipsychotic medications. This pattern remitted only after hormonal therapy was initiated. Through this case report, the authors review the literature on the menstrual psychoses, exemplified by this case, and discuss treatment options and prognosis. Menstrual psychosis is an underrecognized condition where psychotic symptoms recur cyclically with menses. Given the poor response that this entity shows to antipsychotic treatment, hormonal therapies have a prominent role.

A Rationale for Timing of Luteal Support Post Gonadotropin-Releasing Hormone Agonist Trigger.

Gonadotropin-releasing hormone (GnRH) antagonist-based ovarian stimulation protocol is gaining popularity. This protocol allows for the use of GnRH agonist as a trigger of final oocyte maturation, instead of the "gold standard" human chorionic gonadotropin (hCG) trigger. GnRH agonist trigger causes quick luteolysis, hence its widespread use in the context of ovarian hyperstimulation syndrome (OHSS) prevention. To secure pregnancy post GnRH agonist trigger, the luteal phase must be supplemented to counteract the luteolysis. Several luteal phase protocols post GnRH agonist trigger have been suggested, most notably based on increasing luteal luteinizing hormone (LH) activity (by adding LH or hCG). The current review aims at delineating a rationale for timing luteal support with a single hCG bolus post GnRH agonist trigger. The review also suggests a set of simple rules that must be followed when designing luteal phase support post GnRH agonist trigger.

Gonadotropin Releasing Hormone Agonist Final Oocyte Maturation and Human Chorionic Gonadotropin as Exclusive Luteal Support in Normal Responders.

BACKGROUND/AIMS: Gonadotropin releasing hormone (GnRH) agonist triggering results in an endogenous gonadotropin flare. Although it effectively stimulates ovulation, GnRH agonist triggers results in an early luteolysis and requires modification of the luteal support. The current study aims to evaluate GnRH agonist triggering with exclusive human chorionic gonadotropin (hCG) luteal support. METHODS: In this prospective observational study, 56 normogonadotropic-assisted reproductive technology patients, stimulated using a GnRH-antagonist protocol, were studied. Final oocyte maturation was achieved with 0.2 mg triptorelin acetate followed by progesterone free luteal support with human choriogonadotropin (1,500 IU * 2). A control group was selected from a pool of 1,023 normogonadotropic patients who received Choriogonadotropin alfa for final oocyte maturation and progesterone suppositories for luteal support. RESULTS: No significant difference was found for the number of oocytes, oocyte maturation rate, fertilization and implantation rate, clinical pregnancy rate (25 vs. 26.7%) and live birth rate (25 vs. 21.4%). Progesterone levels in conception cycles were significantly higher in the study group than corresponding levels in the control group. CONCLUSION: GnRH agonist triggering with exclusive hCG support may be a valid alternative to hCG triggering with progesterone support. This protocol combines the potential advantages of a physiological trigger with a simple, patient-friendly, luteal support.

Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.

PURPOSE: The 2018 American Urological Association guidelines on the Evaluation and Management of Testosterone Deficiency recommended that 300 ng/dL be used as the threshold for prescribing testosterone replacement therapy (TRT). However, it is not uncommon for men to present with signs and symptoms of testosterone deficiency, despite having testosterone levels greater than 300 ng/dL. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. We sought to evaluate serum testosterone response and duration of therapy of hCG monotherapy for men with symptoms of hypogonadism, but total testosterone levels > 300 ng/dL. MATERIALS AND METHODS: We performed a multi-institutional retrospective case series of men receiving hCG monotherapy for symptomatic hypogonadism. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy. Descriptive analysis was performed and Mann Whitney U Test was utilized for statistical analysis. RESULTS: Of the 20 men included in the study, treatment indications included low libido (45%), lack of energy (50%), and erectile dysfunction (45%). Mean testosterone improved by 49.9% from a baseline of 362 ng/dL (SD 158) to 519.8 ng/dL (SD 265.6), (p=0.006). Median duration of therapy was 8 months (SD 5 months). Fifty percent of patients reported symptom improvement. CONCLUSIONS: Treatment of hypogonadal symptoms with hCG for men who have a baseline testosterone level > 300 ng/dL appears to be safe and effi cacious with no adverse events.

Luteal phase HCG support for unexplained recurrent pregnancy loss - a low hanging fruit?

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies and accounts for only 1-5% of pregnancy failures. Treatment options for unexplained RPL (uRPL) are limited. Previous studies suggest a link between delayed implantation and pregnancy loss. Based on this, a timely signal for rescue of the corpus luteum (CL) using human chorionic gonadotrophin (HCG) could improve outcomes in women with uRPL. This retrospective cohort study included 98 subjects with uRPL: 45 underwent 135 monitored cycles without HCG support; and 53 underwent 142 cycles with a single mid-luteal HCG injection. Based on Log-rank Mantel-Cox survival curves, miscarriage rate and time to pregnancy decreased in the HCG group (P = 0.0005). Women receiving luteal HCG support had an increased chance of an ongoing pregnancy compared with those not receiving it (RR = 2.4; 95% CI 1.4-3.6; number need to treat (NNT) = 7; 95% CI 4-18). Subjects receiving HCG support had a significant absolute risk reduction (ARR) of miscarriage (P < 0.001; ARR = 11.5%; 95% CI 3.6-19.5; NNT = 9(5-27). These data suggest restoration of synchrony and CL support improves outcomes in women with RPL. Further randomized controlled trials of luteal-phase HCG in women with RPL appears warranted.

Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial.

BACKGROUND: Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled ovarian stimulation. Early ovarian hyperstimulation syndrome occurs during luteal phase of controlled ovarian stimulation within 9 days after human chorionic gonadotropin trigger and reflects an acute consequence of this hormone on the ovaries. Late ovarian hyperstimulation syndrome occurs 10 or more days after human chorionic gonadotropin trigger and reflects increased endogenous human chorionic gonadotropin levels following pregnancy. Human chorionic gonadotropin stimulates granulosa-lutein cells to produce vascular endothelial growth factor messenger RNAs, which in turn raises serum vascular endothelial growth factor concentration and increases vascular permeability in women with ovarian hyperstimulation syndrome. Efforts to reduce the incidence and severity of ovarian hyperstimulation syndrome after oocyte retrieval, and in particular primary prevention efforts, are vital to prevent thrombogenesis and other serious complications. OBJECTIVE: The objective of the study was to compare the efficacy of letrozole, an aromatase inhibitor, with aspirin in primary prevention of early ovarian hyperstimulation syndrome and to compare vascular endothelial growth factor levels between groups. STUDY DESIGN: Participants in this prospective randomized trial included 238 participants undergoing cryopreservation of the whole embryos after oocyte retrieval with at least 1 of the following high-risk factors for ovarian hyperstimulation syndrome: oocyte retrieval ≥25; estradiol level ≥5000 pg/mL on the day of human chorionic gonadotropin administration; and clinical or ultrasonographic evidence of ovarian hyperstimulation syndrome on the day of oocyte retrieval, such as ultrasonographic evidence of ascites. After human chorionic gonadotropin triggering, experimental (119 cases) and control (119 cases) groups received letrozole and aspirin, respectively, for 5 days. The 5 categories of ovarian hyperstimulation syndrome include no, yes-mild, yes-moderate, yes-severe, and yes-critical. The primary outcome was the incidence and severity of early ovarian hyperstimulation syndrome. The secondary outcome included vascular endothelial growth factor level both on the second and seventh day after the human chorionic gonadotropin trigger, and clinical and laboratory features of ovarian hyperstimulation syndrome symptoms. RESULTS: The incidence of ovarian hyperstimulation syndrome was significantly higher in women receiving aspirin, compared with letrozole (90.2% vs 80.4%, P = .044). Moderate and severe ovarian hyperstimulation syndrome was also higher in the aspirin group, 45.1%, compared with the letrozole group, 25.0% (P = .002). Moreover, the duration of luteal phase was shortened in letrozole group compared with aspirin group (8.1 ± 1.1 days vs 10.5 ± 1.9 days, P < .001). The vascular endothelial growth factor level was significantly higher in the letrozole-treated group than aspirin-treated group (0.49 ± 0.26 vs 0.42 ± 0.22, P = .029). CONCLUSION: Letrozole was more effective than aspirin in decreasing the incidence of moderate and severe early-onset ovarian hyperstimulation syndrome. Our results indicate that ovarian hyperstimulation syndrome might be caused through a luteolytic effect rather than through modulation of vascular endothelial growth factor, racing by a decline in estradiol and termination of early-onset ovarian hyperstimulation syndrome in advance in high-risk women with cryopreservation of the whole embryos.

The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence.

17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study.

BACKGROUND: Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. OBJECTIVE: Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. STUDY DESIGN: This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17-hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of ≥1 injection of the drug. RESULTS: Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17-hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received ≥1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. CONCLUSION: Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17-hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth.

Hormone-Based Treatments in Subfertile Males.

Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments.

Effects of estradiol injection on outcome of in-vitro fertilization: a randomized, double-blind, placebo controlled trial.

PURPOSE: To evaluate the effects of estradiol (E2) supplementation on pregnancy outcome in patients with unexplained infertility undergoing in vitro fertilization (IVF). MATERIALS AND METHODS: A total of 100 women with unexplained infertility and candidates for IVF, were included in this study and were randomly assigned to receive E2 supplementation or placebo during the luteal phase. The E2 serum levels in the hCG administration day and third and seventh day after ovum retrieval were measured in control group. The rate of pregnancy was also quantified and compared between the two study groups. RESULTS: There was no significant difference between two study groups regarding baseline characteristics. E2 level decreased significantly in third (1765.34 ± 680.09; p < 0.001) and seventh (1459.66 ± 593.80; p < 0.001) days after ovum retrieval (2411.16 ± 713.52). The authors found that the serum level of E2 was significantly lower in those who received E2 supplementation at day 3 (p < 0.001) and 7 (p<0.001). However the pregnancy rate was not significantly different between two study groups (p = 0.849). In the same way, there was no significant difference between two study groups regarding the number of retrieved oocytes (p = 0.563) and number of MII oocytes (p = 0.103). CONCLUSIONS: E2 supplementation during the luteal phase in patients with unexplained infertility undergoing IVF, is associated with decreased serum levels of E2 after hCG injection. However the fertility outcome was not affected by E2 supplementation.

Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive ß-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation.

The individualized choice of embryo transfer timing for patients with elevated serum progesterone level on the HCG day in IVF/ICSI cycles: a prospective randomized clinical study.

This study analyzed the clinical outcomes of patients with elevated progesterone level on the HCG day in IVF/ICSI cycles, with different timing of embryo transfer. A total of 123 patients were involved in this prospective randomized clinical study. Group 1: blastocyst transfer group, 38 cases; Group 2: frozen-thawed embryo transfer group (first FET cycle), 42 cases; Group 3: fresh embryo transfer group, 43 cases. The basal FSH level was comparable among three groups (6.7 ± 3 versus 7.0 ± 2 versus 6.9 ± 2.4, p = 0.897). The clinical pregnancy rate was highest in group 2, lowest in group 3, with significantly difference (31.6% versus 38.1% versus 13.9%, p = 0.037). The implantation rate and live birth rate were still lowest in group 3 (21.9% versus 19.8% versus 6.7%, p = 0.016 and 18.4% versus 31% versus 11.6%, p = 0.081). In conclusion, the elevated progesterone level will affect clinical pregnancy rate in fresh embryo transfer cycles. We suggest frozen-thawed embryo transfer for these patients. However, for those patients who expressed the wish to have fresh embryo transfer, they should be suggested fresh blastocyst transfer, if they have more than five good quality embryos.

Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome.

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PURPOSE: To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. MATERIALS AND METHODS: Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. RESULTS: A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. CONCLUSIONS: A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

The impact of LH, E2, and P level of HCG administration day on outcomes of in vitro fertilization in controlled ovarian hyperstimulation.

OBJECTIVES: The objective of this study was to evaluate the impact of luteinizing hormone (LH), estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) administration on outcomes of in vitro fertilization (IVF) in controlled ovarian hyperstimulation (COH). STUDY DESIGN: In this retrospective study, 129 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments were included; these cycles were stratified according to LH levels of ≥ 1.12 IU/L or < 1.12 U/L and according to E2 levels of ≥ 1,005.89 pmol/L or < 1,005.89 pmol/L. The main outcome measure was the clinical pregnancy rate. RESULTS: The clinical pregnancy rate was significantly higher in the group with LH ≥ 1.12 IU/L than in the group with LH < 1.12 U/L (43.28% vs. 30.65%, p < 0.05). The clinical pregnancy rate was also higher in the group with E2 ≥ 1,005.89 pmol/L than in the group with average E2 < 1,005.89 pmol/L (42.86% vs. 30.51%, p < 0.05). Among the LH, E2, and P levels on the day of HCG administration, LH level was the most important predictor of outcomes of IVF in COH. The present data showed an adverse effect of low serum LH level (LH < 1.12 IU/L) on the day of HCG administration on clinical pregnancy rate. E2 level can also predict the outcomes of IVF in COH. CONCLUSIONS: Low serum LH level (LH < 1.12 IU/L) and low serum E2 level (average E2 < 1,005.89 pmol/L) on the day of HCG administration led to low clinical pregnancy rates, while the P level on the day of HCG administration may have had little effect on clinical pregnancy.